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Updated: Jun 20, 2026

A Flow Cytometry-Based Cell Surface Protein Binding Assay for Assessing Selectivity and Specificity of an Anticancer Aptamer
Published on: September 13, 2022
RNA aptamers interfering with nucleophosmin oligomerization induce apoptosis of cancer cells
1Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Abstract:
Nucleophosmin (NPM) is a multifunctional protein involved in both proliferation and apoptosis. Importantly, NPM negatively regulates p53 and is frequently overexpressed in a wide variety of cancers. To identify inhibitory molecules of NPM, we used an in vitro selection method termed systematic evolution of ligands by exponential enrichment (SELEX) to select RNA aptamers that bind to NPM with high affinity and specificity. The selected RNA aptamers bind to the central acidic region of NPM and affect its oligomerization both in vitro and in vivo. Remarkably, expression of NPM-specific aptamers causes mislocalization of NPM in the nucleoplasm rather than in the nucleolus, suggesting that NPM oligomerization is important for its proper localization. Moreover, p14ARF is mislocalized in the nucleoplasm and p53 is upregulated in cells expressing NPM aptamers. In addition, cancer cells expressing NPM aptamers not only undergo apoptosis on their own, but are more susceptible to apoptosis induced by DNA-damaging agents as well. These results suggest that interfering with NPM oligomerization can inhibit NPM function and aptamers targeting NPM can serve as potential lead for developing anticancer drugs.
Insights
Researchers developed RNA aptamers targeting Nucleophosmin (NPM), a protein overexpressed in cancers. These aptamers disrupt NPM
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Nucleophosmin (NPM) is a key protein regulating cell proliferation and apoptosis.
- NPM negatively controls p53 levels and is often overexpressed in various cancers.
- Identifying molecules that inhibit NPM is crucial for cancer therapy development.
Purpose of the Study:
- To discover novel RNA aptamers with high affinity and specificity for NPM.
- To investigate the functional impact of NPM inhibition on cancer cells.
- To explore the therapeutic potential of NPM-targeting aptamers.
Main Methods:
- Systematic Evolution of Ligands by Exponential Enrichment (SELEX) for aptamer selection.
- In vitro and in vivo assays to assess aptamer binding and effects.
- Analysis of protein localization (NPM, p14ARF) and p53 levels.
- Assessment of cancer cell apoptosis induction and susceptibility.
Main Results:
- Selected RNA aptamers bind to NPM's central acidic region and inhibit its oligomerization.
- NPM aptamers cause mislocalization of NPM and p14ARF from the nucleolus to the nucleoplasm.
- NPM aptamer expression leads to p53 upregulation and increased cancer cell apoptosis.
- Cancer cells with NPM aptamers show enhanced susceptibility to DNA-damaging agents.
Conclusions:
- Interfering with NPM oligomerization effectively inhibits its oncogenic functions.
- NPM-specific aptamers demonstrate potential as a novel therapeutic strategy for cancer.
- Targeting NPM oligomerization offers a promising avenue for developing new anticancer drugs.
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